Concurrent non-ketotic hyperglycinemia and propionic acidemia in an eight year old boy

Paul S Kruszka,Brian Kirmse,Dina J Zand,Kristina Cusmano-Ozog,Elaine Spector,Johan L Van Hove,Kimberly A Chapman

doi:10.1016/j.ymgmr.2014.04.007

Abstract

This is the first reported case of a patient with both non-ketotic hyperglycinemia and propionic acidemia. At 2years of age, the patient was diagnosed with non-ketotic hyperglycinemia by elevated glycine levels and mutations in the GLDC gene (paternal allele: c.1576_1577insC delT and c.1580delGinsCAA; p.S527Tfs*13, and maternal allele: c.1819G>A; p.G607S). At 8years of age after having been placed on ketogenic diet, he became lethargic and had severe metabolic acidosis with ketonuria. Urine organic acid analysis and plasma acylcarnitine profile were consistent with propionic acidemia. He was found to have an apparently homozygous mutation in the PCCB gene: c.49C>A; p.Leu17Met. The patient was also treated with natural protein restriction, carnitine, biotin, and thiamine and had subjective and biochemical improvement.

Highlights

Despite our effort to classify all of an individual's findings under one genetic or metabolic diagnosis, individuals can have more than one disorder
Kruszka et al / Molecular Genetics and Metabolism Reports 1 (2014) 237–240 biochemical cause and pursue further evaluations to examine more than one cause explaining findings in a single patient? Here, we present a patient who has non-ketotic hyperglycinemia (NKH) and a delayed diagnosis of propionic acidemia (PA)
Our patient passed away at home 1 week after the procedure of an unknown cause. He was biochemically stable at discharge. This patient presented with attenuated classic non-ketotic hyperglycinemia which was late onset, should lead to mild developmental delay, a seizure disorder and chorea since it was caused by a typically mild missense mutation identified in GLDC

Summary

Introduction

Despite our effort to classify all of an individual's findings under one genetic or metabolic diagnosis, individuals can have more than one disorder. We present a patient who has non-ketotic hyperglycinemia (NKH) and a delayed diagnosis of propionic acidemia (PA). Ketotic hyperglycinemia, predominately caused by the organic acidurias, propionic acidemia, (PA, from mutations in the genes PCCA and PCCB) and the methylmalonic acidurias (MMAs), presents with increased ketones in urine and serum [2]. Individuals with PA have characteristic elevations in the organic acids, 3-hydroxypropionic acid and methylcitrate, but can have increased plasma glycine levels. These individuals usually present with ketoacidosis and symptoms such as lethargy, vomiting and can develop coma [2,3]. But usually during acidosis episodes [4]

Case report

Discussion