Propionic acidemia is a rare, autosomal recessive, inherited inborn error
of propionate metabolism presenting as life threatening ketoacidosis
progressing rapidly to coma and death [1]. Very few cases presenting with
hyperglycemia have been described [2,3].
We report a 11 month old girl with propionic acidemia
appearing as diabetic ketoacidosis. This child was referred to us for
further care with diagnosis of diabetic ketoacidosis. Before coming to us
she was admitted with fever, breathlessness and altered sensorium. There
was history of failure to thrive and frequent vomiting. She was drowsy and
had acidotic breathing, weak peripheral pulses and delayed capillary
refill. Investigations revealed hemoglobin of 8.7 g/dL, normal WBC and
differential count and low platelet count of 57000/cmm. The blood glucose
was 466 mg/dL and urine ketones. Blood gas revealed severe metabolic
acidosis (pH were positive -7.18, bicarbonate -4.4 mmol/) with increased
anion gap and increased serum lactate. Glycosylated Hb was high (16.2%).
She received treatment with insulin drip, IV fluids and antibiotics.
Acidosis and sensorium improved over the next 24 hours after which she was
referred to our institution. She weighed 6 kg (<3rd centile) and measured
72 cm in length. She was given subcutaneous regular insulin of 0.5
u/kg/day with daily monitoring of blood glucose. Insulin had to be
gradually decreased and then stopped within 7 days as she had frequent
hypoglycemia. She was re-admitted within 7 days for vomiting, dehydration,
tachypnea and drowsiness . Investigations revealed WBC of 3400/cmm with
normal platelet count , metabolic acidosis, blood glucose of 349 mg%,
urine positive for ketones and high serum ammonia of 202 mcg/dL. She was
treated with IV fluids and subcutaneous insulin after which she improved
within 24 hours. Urine was analysed with a suspicion of organic acidemia
by gas chromatography/mass spectrometry, revealed increased excretion of
glycine, 3-hydroxypropionic acid, 3-hydroxybutyric acid,
3-hydroxyvalerate, propionyl glycine, tiglylglycine and methylcitrate,
which are the biochemical marker compounds of propionic acidemia. Biotin
(10mg) and carnitine was added to the therapy and diet with low proteins
(1 g/kg/day) was given.
Our initial diagnosis in this patient was type 1
diabetis mellitus. However, rapid response and recurrent hypoglycemia on
insulin therapy, leucopenia, thrombocytopenia and hyperammo-nemia made us
suspect an organic acidemia. Most patients with propionic acidemia present
with acute episodes of metabolic acidosis, hypoglycemia, hyperammonemia
and characteristic organic aciduria due to the decreased activity of
intra-mitochondrial enzyme propionyl CoA carboxylase before they are a few
months old.
In our patient, severe hyperglycemia with ketoacidosis
was the first life threatening presentation of propionic acidemia to
emphasize that hyperglycemia with ketoacidosis is not always diabetes. One
should think of propionic acidemia, especially if there is young age of
presentation, hyperammonemia, leukopenia, thrombocytopenia and insulin
therapy gets withdrawn rapidly.
References
1. Wayne AF, Leon ER. Disorders of propionate and
methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS,
Valle D, eds. Metabolic and Molecular Basis of Inherited Disease. 7th Edn.
Vol 1. Philadelphia: McGraw –Hill; Philadelphia. 1995.p. 1431-4.
2. Lehnert W, Junker A, Wehinger H, Zoberlein HG,
Baumgartner R, Ropers HH. Propionic acidemia associated with
hypertrophic pyloric stenosis and bouts of severe hyperglycemia.
Monatsschr Kinderheilkd. 1980;128:720-3.
3. Dweikat IM, Naser EN, Abu Libdeh AI, Naser OJ, Abu
Gharbieh NN, Maraqa NF, et al. Propionic acidemia mimicking
diabetic ketoacidosis. Brain Dev. July 13, 2010 [Epub ahead of print].
4. Jean MS, Christiane C. Clinical Phenotypes:
Diagnosis/Algorithms. In: Scriver CR, Beaudet AL, SLY WS, Valle D,
eds. Metabolic and Molecular Basis of Inherited Disease,7th Edn. Vol 1.
Philadelphia. McGraw-Hill; 1995.p. 334-40.