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Year : 2020  |  Volume : 7  |  Issue : 4  |  Page : 209-213

Propionic acidemia presenting as encephalopathy, hyper-ammonemia, recurrent pulmonary hemorrhage: A case report

1 Department of Pediatrics, Aditya Birla Memorial Hospital, Chinchwad, Pune, Maharashtra, India
2 Department of Pediatrics, Dr. Bidari's Ashwini Hospital & Post-graduation Center, Vijaypura, Karnataka, India

Date of Submission15-Apr-2020
Date of Decision07-May-2020
Date of Acceptance19-May-2020
Date of Web Publication13-Jul-2020

Correspondence Address:
Dr. Ramaning Loni
Aditya Birla Memorial Hospital, Thergaon, Chinchwad, Pune - 411 033, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JPCC.JPCC_57_20

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The metabolic crisis due to inborn error of metabolism can present as an isolated entity or along with the underlying sepsis at any age in children. Here, we present 14 months old boy born of third-degree consanguinity, apparently healthy in the past, admitted with encephalopathy, low GCS, hyperammonemia, and recurrent pulmonary hemorrhage in our hospital, requiring initial resuscitation with stabilization of airway, breathing, circulation, and disability. He required neuroprotective measures including intubation, ventilation with hyperosmolar therapy, and vasoactive drug infusion through the femoral central line for the shock due to metabolic crisis. His urine gas chromatography/mass spectroscopy (MS) for organic acids analysis and blood tandem MS for the plasma amino acids profile, carnitine, and acylcarnitine profile suggested propionic acidaemia, which is rare autosomal recessive disorder and he required dietary modification with metabolic cocktail therapy through a central line with peritoneal dialysis initially for hyperammonemia but subsequently requiring renal replacement therapy to decrease the raised ammonia levels, gradually his sensorium improved, extubated, and sent home with inborn error of metabolism oral cocktail therapy but a few days later, he succumbed to death.

Keywords: Inborn errors of metabolism, metabolic crisis, propionic acidemia, pulmonary hemorrhage

How to cite this article:
Loni R, Tapal S, Anita B, Kamale M, Bidari LH. Propionic acidemia presenting as encephalopathy, hyper-ammonemia, recurrent pulmonary hemorrhage: A case report. J Pediatr Crit Care 2020;7:209-13

How to cite this URL:
Loni R, Tapal S, Anita B, Kamale M, Bidari LH. Propionic acidemia presenting as encephalopathy, hyper-ammonemia, recurrent pulmonary hemorrhage: A case report. J Pediatr Crit Care [serial online] 2020 [cited 2020 Aug 9];7:209-13. Available from: http://www.jpcc.org.in/text.asp?2020/7/4/209/289525

  Introduction Top

Inborn errors of metabolism (IEM) are a group of rare genetic (inherited) disorders usually due to defect in specific proteins (enzymes) or transport proteins and or may be due to excessive storage of intermediate metabolites, which causes a block in the metabolic pathway.[1],[2] The incidence of IEM is collectively estimated to be as high as 1:800 live births.[3] Propionic acidemia is a rare metabolic disorder characterized by the deficiency of propionyl CoA carboxylase, an enzyme involved in the breakdown of building blocks (amino acids) of certain proteins.[4] It usually presents in the first few weeks of life in the form of hypotonia, poor feeding, vomiting, lethargy, dehydration, and episodes of uncontrolled seizures. The prevalence of propionic acidemia all over the world is 1; 105,000–1:25,000 and it is more prevalent in Saudi Arabian tribes and Greenlandic.[5]

The gene for alpha subunit, Propionyl CoA carboxylase alpha (PCCA) and beta subunits, Propionyl CoA carboxylase beta (PCCB) are located on chromosome 13q32.3 and Chromosome 3q22.3 respectively.[5] Any mutations in these genes PCCA and PCCB would result in propionic acidemia. Here, we present 14 months old boy who has presenting with encephalopathy, recurrent pulmonary bleed, hyperammonemia with high anion gap metabolic acidosis requiring both peritoneal dialysis, and sustained low-efficiency daily dialysis (SLEDD) in peripheral set up is unique.

  Case Report Top

A 14-months-old boy, born of third-degree consanguineous marriage admitted with a history of loose stools, vomiting, excessive lethargicness for the past 3–4 days. On admission, the child was encephalopathic with low GCS of 3/15 with pinpoint pupils, generalized hypotonia, absent deep tendon reflexes, acidotic breathing, with signs of poor perfusion in the form of cold extremities with delayed capillary refill time, and hepatomegaly. Blood investigations showed a pancytopenia picture (Hb7 g%, white blood cell 2800 cells/mm3, PLT 1.1 lakhs cells/mm3) with normal liver function. arterial blood gas (ABG) on admission (pH <6.8/PaCO2–21 mmHg/PaO2 =87 mmHg/HCO3 not recordable) suggestive of severe high anion gap metabolic acidosis (AG 47), without ketosis with moderate hyperammonemia (ammonia 194 mmol/L), normal lactate (1.4 mmol/L) and normal blood glucose levels. Initial differential diagnosis was probable Organophosphorus poisoning/stroke with nonconvulsive status epilepticus/IEM with the metabolic crisis. The blood sample was sent for tandem mass spectroscopy (TMS) of serum amino acids, carnitine, and acylcarnitine profile and urine sample for gas chromatography-mass spectroscopy (GC-MSS) for organic acids profile was sent and IEM cocktail (Injection Carnitine, Injection Multivitamin, tablet coenzyme Q, Tablet Biotin, Injection Methylcobalamin, L-arginine sachet added along with sodium benzoate enterally through nasogastric tube) was started after initial resuscitation of the child with stabilization of the airway, breathing and circulation on day 1 of admission. The IEM workup came after 1 week of hospitalization showed normal serum amino acid levels, low normal free carnitine level (11.069 m Mol/L), and significant elevation of C3 acylcarnitine (Propionyl-carnitine, C3 14.668 m mol/L) in acylcarnitine profile of blood report of TMS. Urine GC/MS report for organic acids showing significant elevations of 3-hydroxy propionate-2 (7.08 mmol/L, propionyl glycine-1 (5.78 mmol/L), tiglyl glycine-1n (8.21 mmol/L), and methyl citrate-4 (1) 50.01 mmol/L, methyl citrate-4 (2) 22.67 micromol/L) levels so both suggestive of propionic acidemia. The child was intubated and ventilated thrice, the first time in view of low GCS (E1M2V1) for neuroprotection for 4 days, and again 2nd time two times for massive pulmonary hemorrhage, each time lasting for 5 days. Two sessions of peritoneal dialysis was done in view of metabolic encephalopathy with hyperammonemia. The child's sensorium improved as serum ammonia decreased to 49 mmol/L. Chest X-ray is done after extubation suggestive of the right upper lobe consolidation probably due to aspiration. In view of persisting fever spikes, IV antibiotics were upgraded. The child was started on heated humidified high flow nasal cannula postextubation. He was reintubated in view of worsening respiratory distress and altered sensorium, and again repeat serum ammonia was 106 mmol/L. In the view of underlying unstable hemodynamic status, small child, and peritoneal dialysis restarted after nephrology consultation. Serum ammonia levels decreased, but peritoneal dialysis was stopped for the development of peritonitis (560 cells, N70%, L30%). PD fluid culture grew acinetobacter baumanii complex sensitive to Injection Colistin and Injection Polymyxin B. Antibiotics changed according to the sensitivity pattern. However, the child was inserted femoral 8.5 Fr HD catheter for SLEDD for the next 3 days. He tolerated the procedure well with some underlying vasoactive drug support.

The child persistently had thrombocytopenia, so antifungal drugs (injection fluconazole) were added. Serum ammonia repeated showing increasing trend with normal renal function. The liver function test was done, suggestive of hypo-albuminemia with mild deranged PT, INR, and APTT, for which two aliquots of injection Human albumin 20% was transfused slowly. In view of deranged coagulation profile, pack cell RBC and fresh frozen plasma were transfused. SLEDD started in view of progressively increasing serum ammonia and altered sensorium. After two cycles of SLEDD, serum ammonia was reduced to 26 mmol/L. The child had insidious onset profuse pulmonary bleed followed by cardiac arrest, child resuscitated, revived and reintubated, and continued ventilation for another 5 days and extubated after that. The child was discharged on oral IEM cocktail medications, which included oral carnitine, sodium bicarbonate suspension. The child succumbed to death after 12 days after discharge at home as expected.

  Discussion Top

Propionic academia is a rare autosomal recessive trait, with the most common presentations in neonatal and early infancy are poor feeding, vomiting, lethargy, seizure, hypotonia. Neurological manifestations include moderate-to-severe intellectual disability. Laboratory findings of severe metabolic acidosis with high anion gap metabolic acidosis, ketosis, neutropenia, thrombocytopenia, hypoglycemia, and hyperammonemia are common during the acute metabolic crisis. The development of Acinetobacter baumanii peritonitis and sepsis has contributed to the disseminated intravascular coagulation (DIC) picture along with background pancytopenia and persistent thrombocytopenia in the child. Although, thrombocytopenia is well-known entity. Severe thrombocytopenia is a hallmark of the metabolic crisis. However, the massive pulmonary hemorrhage which has happened in our case could be due to underlying sepsis, DIC and thrombocytopenia Magnetic resonance imaging (MRI) of the brain show brain atrophy, basal ganglia involvement including white matter [Figure 1]. EEG shows abnormal left frontocentral epileptic discharges [Figure 2]. In one study,[6] prospective observation study of propionic acidemia in children, 70% of them had abnormal findings in the brain MRI, 40% had brain atrophy, 40% had white matter involvement, and 30% had globus pallidus involvement.
Figure 1: Magnetic resonance imaging of the brain shows a bilateral enlargement of the globus pallidus (a part of basal ganglia)

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Figure 2: (a-d) Electroencephalogram shows spike-wave discharges

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Index child has presented with loose stools, vomiting, lethargy, and hypotonia. Inborn error of metabolism was suspected, and the child had elevated serum ammonia with a normal lactate level. ABG was suggestive of high anion gap severe metabolic acidosis. The diagnosis was confirmed by screening urine samples for organic acids profile by GC/MS test, and blood sample for TMS analysis of serum amino acids, carnitine, and acylcarnitine profile [Figure 3]. After establishing the diagnosis, the child was treated with a low protein diet (0.75 g/kg/day) initially, and metabolic cocktail therapy such as injection Carnitine 200 mg/kg/day, sodium benzoate 250–500 mg/kg/day, high dose Vitamin B12 and folic acid, injection sodium bicarbonate 7.5%, Tablet Co-Q 30 mg BD, tablet biotin 10 mg/day, and syrup metronidazole (10–20 mg/kg/day). The child required peritoneal dialysis and SLEDD [Figure 4] for hyperammonemia, after renal replacement therapy (RRT) therapy, serum ammonia level decreased. The outcome of patients is highly variable. Death is reported in 30% of cases during an initial presentation during early infancy, and in 40% during the subsequent crisis. The rest have a mild course. Hence, in our child, maybe the mild variety of Propionic acidemia, which has decompensated due to intercurrent illness with fasting. Prenatal diagnosis can be made by measuring enzyme activity in cultured amniotic cells or chorionic villi or by identification of the mutant gene, which very crucial for preventing economical, emotional burden. Prognosis of propionic acidemia is very poor; patients with severe disease forms will die in the newborn period itself or later in the infancy due to metabolic decompensation, cardiac complication (cardiomyopathy and arrhythmias), or basal ganglia stroke.[2],[7],[8] The mild LV dysfunction in the index child could be due to the underlying severe metabolic acidosis, septic shock but LV function improved on discharge from the hospital which was done by in house cardiologist. The child was started on long-term low-protein diet (around 1 g/kg/day) but calorie-rich diet with oral L-carnitine 100 mg/kg/day along with oral methylcobalamin, folic acid, and oral biotin therapy till genetic workup is done. Genetic workup for PCCA and PCCB gene mutation study was planned during further follow-up in Outpatient Department, but the child succumbed to death before the next follow-up for genetic workup.
Figure 3: Blood tandem mass spectroscopy for amino acid profile showed low normal free carnitine, Acylcarnitine profile showed elevated serum pripionylcarnitine, C3 level, and urine gas chromatography-mass spectroscopy for organic acids profile showed significant elevations of 3-Hydroxy propionate, propionyl glycine, tiglyl glycine, and methyl citrate levels

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Figure 4: Picture of the same child on sustained low-efficiency daily dialysis and ventilator (Taken due permission from parents)

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The special thing about this study is that child needed prolonged RRT for hyperammonaemia. Another interesting observation, in this case, is the occurrence of massive pulmonary hemorrhage requiring reintubation and ventilation. Pulmonary hemorrhage can be attributed to sepsis, thrombocytopenia, and deranged coagulation profile; however, in late presentation of propionic academia, symptoms vary considerably affecting different organ systems. Early diagnosis and institution of therapy, as done in this case study, is very crucial because neurological outcomes are strongly influenced by the duration of coma and peak concentrations of ammonia. Although in this case, peritoneal dialysis was used as an initial measure for ammonia detoxification, the patient subsequently required more advanced modality such as SLEDD.

What this study will add to the current knowledge is that prevention is better than cure, so prenatal diagnosis by chorionic villus sampling and genetic studies will help in the high-risk population. The universal newborn screening will definitely help in early diagnosis and treatment and improved survival, but no significant difference in adverse long-term outcomes could be shown.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


Thanks to my parents and family for continuous support.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Camp KM, Lloyd-Puryear MA, Yao L, Groft SC, Parisi MA, Mulberg A, et al. Expanding research to provide an evidence base for nutritional interventions for the management of inborn errors of metabolism. Mol Genet Metab 2013;109:319-28.   Back to cited text no. 1
Mak CM, Lee HC, Chan AY, Lam CW. Inborn errors of metabolism and expanded newborn screening: Review and update. Crit Rev Clin Lab Sci 2013;50:142-62.  Back to cited text no. 2
Thomas E. Dietary management of inborn errors of amino acid metabolism with protein-modified diets. J Child Neurol 1992;7(Suppl):S92-Slll.  Back to cited text no. 3
Kliegman Robert M, ST Geme Joseph W, Blum Nathan J, Samir SS, Tasker Robert C, Wilson Kareen M. Nelson Textbook of Paediatrics. 21st ed. Philadelphia: Elsevier, 2020. p. 715-7.  Back to cited text no. 4
Karimzadeh P, Jafari N, Ahmad Abadi F, Jabbedari S, Taghdiri MM, Alaee MR, et al. Propionic acidemia: diagnosis and neuroimaging findings of this neurometabolic disorder. Iran J Child Neurol 2014;8:58-61.  Back to cited text no. 5
Shchelochkov OA, Carrillo N, Venditti C. Propionic acidemia. In: Adam MP, Ardinger HH, Pagon RA GeneReviews. Seattle, WA: University of Washington; 1993.  Back to cited text no. 6
Rousson R, Guibaud P. Long term outcome of organic acidurias: survey of 105 French cases (1967–1983) J Inherit Metab Dis. 1984;7:10-12. doi: 10.1007/BF03047366.   Back to cited text no. 7
Almási T, Guey LT, Lukacs C, Csetneki K, Vokó Z, Zelei T. Systematic literature review and meta-analysis on the epidemiology of propionic acidemia. Orphanet J Rare Dis 2019;14:40. doi:10.1186/s13023-018-0987-z.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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