New disease-modifying treatments have recently been approved for 5q spinal muscular atrophy (SMA) and early treatment has been associated with a better clinical outcome. Accordingly, new-born screening (NBS) for SMA should be implemented to ensure early diagnosis of affected individuals. The aim of this study was to determine the feasibility and usefulness of NBS for SMA in Latvia. Between February and November of 2021, 10,411 parents consented to participation in the study. DNA testing for the SMN1 exon 7 homozygous deletion was conducted using qPCR with fluorescent locked nucleic acid primers. In the first month of testing, reporting of results took up to a maximum of 17 days after samples arrived in the laboratory. However, following familiarisation with the procedure, the median report time was reduced to 11 days after birth. Forty cases required samples to be taken again due to poor quality of the isolated DNA transpiring from either the quality of the blood punch or manual mistakes during DNA isolation. The SMN1 exon 7 homozygous deletion was identified in two individuals, which was subsequently confirmed by multiplex ligation-dependent probe amplification. When a NBS sample is taken 48 to 72 h after birth and transported to the laboratory within two working days after collection according to legal requirements, DNA test results can be reported to healthcare professionals before the 12th day of life. Expansion of our SMA 5q NBS procedure to the whole of Latvia is feasible and would facilitate early diagnosis and result in more effective treatment. We strongly advocate that SMA is added to the national Latvia Recommended Uniform Screening Panel.
There are recent reports of associations of variants in the HPDL gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the HPDL gene was detected in each proband; however, there was no known parental consanguinity. We also highlight reductions in citrate synthase and mitochondrial complex I activity detected in both probands in different tissues, reflecting the previously proposed mitochondrial nature of disease pathogenesis associated with HPDL mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.
Background currently, there are only a few published case reports detailing an increased nuchal translucency (NT) measurement in association with a diagnosis of SMA in the foetus. However, an increased NT measurement is a clinically relevant sign as it can be related to genetic syndromes, foetal malformations, disruptions and dysplasias. This case report highlights the prenatal signs and symptoms in relation to type 0 SMA. Case presentation: this case report presents the first registered patient in Latvia with type 0 spinal muscular atrophy (SMA). The index case was a Caucasian male infant from non-consanguineous parents. During the first-trimester ultrasonography of the unborn patient, an increased thickness of the nuchal fold was detected. The mother reported decreased foetal movements during the pregnancy. After the boy was born, his general condition was extremely severe. The clinical signs indicated a suspected neuromuscular disorder. A precise diagnosis – type 0 SMA – was determined 7 days after birth through a newborn pilot-screening for SMA. The condition of the infant deteriorated. He had severe respiratory distress followed by multiple events leading to death. Conclusions since there are no treatment options for infants with type 0 SMA at present, it is vital to be able to detect this disease prenatally in order to provide the best possible care for the patient and parents. Employment of extensive panel genetic testing using next-generation sequencing would be beneficial for prenatal diagnosis of type 0 SMA cases. Moreover, sequencing of foetal exomes covering single nucleotide variations and copy number variations (also SMN1) offers a broader diagnostic capacity for pregnancies with unexpected foetal anomalies, thus improving both diagnostic timing and counselling for parents. Early recognition of the disease would give parents time to come to terms with the situation, as well as provide the option of pregnancy termination.
This case report presents the first registered patient in Latvia with type 0 spinal muscular atrophy (SMA). During the first-trimester ultrasonography of the unborn patient, an increased thickness of the nuchal fold was detected. The mother reported decreased foetal movements during the pregnancy. After the boy was born, his general condition was extremely severe. The clinical signs indicated a suspected neuromuscular disorder. A precise diagnosis, type 0 SMA, was determined 7 days after birth through a newborn pilot-screening for SMA, which was conducted for all newborns whose parents consented to participate. The condition of the infant deteriorated. He had severe respiratory distress followed by multiple events leading to his death. Currently, there are only a few published case reports detailing an increased nuchal translucency (NT) measurement in association with a diagnosis of SMA in the foetus. However, an increased NT measurement is a clinically relevant sign as it can be related to genetic syndromes, foetal malformations, disruptions, and dysplasias. Since there is no cure for infants with type 0 SMA at present, it is crucial to be able to detect this disease prenatally in order to provide the best possible care for the patient and parents. This includes the provision of palliative care for the patient, among other measures. This case report highlights the prenatal signs and symptoms in relation to type 0 SMA.
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