Outcome of Nonketotic Hyperglycinemia in Lebanon: 14-Year Retrospective Review

Abstract

Nonketotic hyperglycinemia is a rare inborn error of glycine metabolism characterized by a severe metabolic encephalopathy with drug-resistant seizures. Here, we report the outcome of nonketotic hyperglycinemia in a cohort of patients diagnosed and followed-up at a tertiary care reference center in Lebanon, between 2000 and 2014.Eight out of 12 patients with nonketotic hyperglycinemia were retrospectively reviewed. The remainders were excluded for incomplete data. The majority of cases presented with seizures and hypsarrhythmia or burst suppression patterns. Half of the patients died. Survival varied between 7 days and 18 years. Seizures remained unresponsive with poor outcome, despite standard supportive care and antiepileptic therapy; however, two patients were responsive to ketogenic diet and one of them became seizure-free.Scarce data on the outcome of nonketotic hyperglycinemia patients from the Middle East and North Africa region are available. The ketogenic diet, in combination with standard therapies, appears to be effective in controlling the seizures in this devastating disorder. Larger multicenter studies are still needed to establish the role of the ketogenic diet in nonketotic hyperglycinemia.

A Newborn Infant With Poor Feeding: Non-ketotic Hyperglycinemia

“…Standard treatment strategies include the reduction of the plasma concentration of glycine, the use of N-methyl-D-aspartate (NMDA) receptor site antagonists, and the symptomatic care to control intractable seizures in addition to antiepileptic drugs. 7 The current study presented a new case of NKH.…”

Nonketotic Hyperglycinemia: Insight into Current Therapies

“…Attempts to use the above-mentioned therapy resulted in a different clinical response in patients or a complete lack of response, which raises doubts as to the validity of the therapy. In some patients with the classical variant of NKH, no clinical improvement was observed despite the early use of sodium benzoate and/or dextromethorphan, even if a reduction in glycine plasma concentration was temporarily achieved [ 3 , 16 , 17 ]. The wide variation in therapeutic effects may be influenced by the heterogeneity of NKH-inducing mutations, which has not always been considered [ 8 ].…”

“…Similarly, Kava et al achieved a significant reduction in seizure frequency and in antiepileptic drug use in a patient with epileptic encephalopathy with several seizure types, including flexor spasms, multifocal clonic and myoclonic seizures [ 26 ]. In addition, lowering glycine levels, improving tonic spasm and tonic-clonic seizure control and complete resolution of tonic-clonic seizures when the KD was used were also reported [ 3 ]. It has been shown that the use of this diet can bring benefits even in NKH patients with very severe forms of seizures, including the resolution of super-refractory status epilepticus (SRSE) [ 42 ].…”

“…The KD significantly increases the comfort of life and reduces the number of hospitalizations by improving the control of epileptic seizures. Some patients reported a complete reduction in epileptic seizures or a reduction in the number of AEDs [ 3 , 16 , 26 ]. This may be of particular importance to the families of patients with severe NKH, for whom therapeutic strategies that affect the quality of life are severely limited.…”

“…Hypotonia is the most common symptom. Attenuated NKH is more often reported in patients that developed symptoms when over three months of age [ 1 , 3 , 4 ].…”